The proposed work seeks to delineate central nervous system pathways involved in the analgesia produced by non-narcotic agents and to determine if these pathways overlap with those activated during opiate-induced analgesia. The initial strategy has been to microinject non-narcotic analgesic agents, shown to cause analgesia when given systemically, into specific brain nuclei which are active areas for morphine analgesia. We have thus far focussed our attention on the dibutyryl derivatives of the adenosine and guanosine cyclic nucleotides (db cAMP, db cGMP) which cause analgesia (or to modify the analgesic action of systemically administered morphine) when administered to the whole brain. db cGMP produced analgesia following local injection into the periaqueductal gray (PAG) and caudal reticular formation (CRF), both active areas for opiate analgesia. db cGMP caused analgesia when injected into the CRF but not in the PAG. These data suggest there is some overlap of neuronal substrates activated during analgesia caused by opiates with those activated during analgesia induced by cyclic nucleotides. These data, however, do not support the hypothesis that suppression of adenylate cyclase is involved in the mechanism of morphine analgesia; if this were the case then administration of db cAMP should reduce and not elevate nociceptive threshold, as observed.